Establishment of patient-derived cancer xenografts in immunodeficient NOG mice

Abstract

Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called ‘cancer xenopatients’) are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001). In our PDX models, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In eight cases (7%), the transplantable xenografts for several generations were composed of large monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus infection-associated lymphoproliferative lesions. Despite this, PDX linked with clinical information offer many advantages for preclinical studies investigating new anticancer drugs. The fast and efficient establishment of individual PDX may also contribute to future personalized anticancer therapies.

Modeling of Patient-Derived Xenografts in Colorectal Cancer

“…In the case of one CRC study, approximately 70% of patient samples grafts developed a PDX (22). Anecdotal practices, speculative factors and limited experimental findings in other tumor types support the notion that engraftment rates are affected by several factors, including tumor type, tissue source, cancer stage, tumor grade, tumor molecular characteristics, acquisition strategy, exposure to prior radiation or systemic chemotherapy, and technical manipulations during grafting (such as time to implantation) (30–33). In this study, we established a large cohort of PDX models derived from both surgical and biopsy specimens to systematically examine whether these factors effect engraftment in PDX models.…”

Organoid of ovarian cancer: genomic analysis and drug screening

“…Considering that precision medicine emphasizes the importance of patient-derived models, researchers have upgraded cell line xenotransplantation models and called them PDX. Fresh tumor cells or tissues of resected patients were implanted into the immunodeficient mice, PDX, to preserve genome integrity and tumor heterogeneity [10,11]. PDX transplants the patient's tumor fragments into immunodeficient mice and can be used for resected tissue, biopsy, ascites/pleural effusion, and pleural sampling.…”

High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer

“…176). Tumor tissues from surgical specimens removed from patients with pancreatic cancer were transplanted subcutaneously into 6-12-week-old NSG mice using transplantation needles (S1A Fig) [16,17]. The details of patients with pancreatic cancer whose tumor tissues were used to generate the PDX mouse models are shown in S1 Table. All mice received the anesthesia with inhaled isoflurane, and euthanasia was performed by cervical dislocation before tumor tissues were excised.…”